The invention relates to a novel pharmaceutical composition containing as the active ingredient a compound of formula I: ##STR2## wherein R is OH or COOH,
or one of its pharmacologically acceptable salts, in the form of an inclusion in pregelatinized starch, which can contain at least one other adjunct as an active or inactive component. PA1 Particle size: at least 90%&lt;150 .mu. PA1 Bulk volume: 1.6 ml/g PA1 Tamped volume: 1.3 ml/g PA1 Fraction soluble in cold water: 10-20% PA1 Loss on drying: maximum 14% PA1 pH of a dispersion in water: 4.5-7
The compounds of formula I include roxindol (I, R=OH; compare European patent 281 608 which corresponds to U.S. Pat. No. 4,914,114) and carmoxirol (I, R=COOH; compare European patent 144 012 which corresponds to U.S. Ser. No. 07/674,635 now U.S. Pat. No. 5,069,794). They can also be used in the form of their pharmacologically acceptable salts, especially their acid addition salts or, in the case of carmoxirol, also their salts with bases. Acid addition salts which can be used are salts with inorganic acids, for example with sulfuric acid, nitric acid, hydrohalic acids such as hydrochloric acid or hydrobromic acid, phosphorus acids such as orthophosphoric acid, and sulfamic acid, and salts with organic acids, especially with aliphatic, alicyclic, araliphatic, aromatic or heterocyclic monobasic or polybasic carboxylic, sulfonic or sulfuric acids, for example formic acid, acetic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, furamic acid, maleic acid, lactic acid, tartaric acid, malic acid, benzoic acid, salicylic acid, 2- or 3-phenylpropionic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methdne- or ethane-sulfonic acid, ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalene-monosulfonic and -disulfonic acids and laurylsulfuric acid. Roxindol is preferably used in the form of the methanesulfonate and carmoxirol in the form of the hydrochloride.
For carmoxirol, possible salts with bases are especially the sodium, potassium, magnesium, calcium and ammonium salts, as well as substituted ammonium salts, for example the dimethyl-, diethyl- or diisopropylammonium, monoethanol-, diethanol- and triethanolammonium, cyclohexylammonium, dicyclohexylammonium and dibenzylethylenediammonium salts.
Roxindol is a dopamine agonist and is used as a neuroleptic. Carmoxirol is a dopaminergic hypotensive.
However, attempts to prepare durable and reproducibly stable pharmaceutical formulations of roxindol and carmoxirol, especially for oral administration, met with considerable difficulties. Thus this object could not be achieved with quite a number of conventional methods: preparation of granules, for example with lactose hydrate, mannitol or microcrystalline cellulose as the filler, especially also using solutions of cellulose ethers or gelatin; inclusions in gelatin with subsequent addition of fillers; absorption of he active ingredients from solution, for example on to lactose hydrate, mannitol or microcrystalline cellulose; and trituration of the active ingredients with lactose hydrate or pregelatinized maize starch.
Attempts to stabilize said formulations with antioxidants such as ascorbic acid, tocopherol or tocopherol derivatives, or with citric acid, did not give the desired result either.